A newly-recognized population of residual neural crest cells in the adult leptomeninges is re-activated for vascular repair
Nakamura, Y.; Nakano, T.; Park, J.-H.; Tanaka, M.; Li, W.; Esposito, E.; Ahn, B.-J.; Duran-Laforet, V.; Desai, R.; Sencan, I.; Sakadzic, S.; Lo, E.; Snyder, E.; Tabaka, M.; Hayakawa, K.
Show abstract
The neural crest (NC) is a transient structure in vertebrate embryogenesis comprising highly migratory multipotent stem cells that give rise to a diverse array of cell types in organs throughout the body, including initiating neurovascular patterning. It is assumed that neural crest stem cells (NCSCs) disappear after development. Unexpectedly, using single-nucleus RNA-sequencing, we discovered residual quiescent NCSCs in the adult mouse meninges which are activated by injury and contribute to the brains homeostatic response. RNA velocity, pathway, and transcription factor analyses in a murine stroke model (combined with in vivo imaging) show that these adult NCSCs migrate towards the perivascular spaces of the infarct and undergo a perivascular stromal cell transition that is regulated by Ptp1b, Ghr, and Stat3. Loss- and gain-of-function experiments show that these "vestigial" NCSCs are required for restoring vascular endothelial barrier function via {beta}-catenin and Stat3 signaling. These findings suggest that, in the adult, an unexpected reservoir of cells -- once pivotal to embryogenesis and vascular morphogenesis -- are re-invoked for neurovascular repair.
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